Project Abstract The human wrist, which positions the hand to accomplish many essential tasks of daily living, provides three degrees of freedom (DOFs): rotation, flexion/extension, and ulnar/radial deviation. Current powered prosthetic wrists provide only wrist rotation; no available powered device provides wrist extension/flexion, which likely reduces the functional ability of individuals with transradial amputations. We have developed a robust 2-DOF wrist that provides independently controlled rotation and extension/flexion; we proposed to conduct a phase 1 clinical trial to determine whether this wrist provides better functional performance than a 1-DOF wrist (rotation only). In addition, we have developed a pattern recognition (PR)-based control system, now commercially available, which will be used to control devices in this trial. PR of electromyographic (EMG) signals from the residual limb provides seamless sequential control of arm DOFs, making control easier and more intuitive than conventional myoelectric control systems that require the user to switch the prosthesis into different modes to control different DOFs. However, current PR systems do not allow the simultaneous control of DOFs provided by an intact arm. We have developed a new PR algorithm, based on a novel control method called probabilistic weighted regression that, in preliminary studies, has demonstrated robust control of a multi-DOF prosthesis. Thus we will also evaluate the functional benefits of simultaneous PR control compared to sequential PR control. We will recruit up to 20 individuals with mid-length, unilateral transradial amputations to participate in the trial, anticipating that at least 14 subjects will complete all three aims. For Aim 1 we will fit participants with a prosthesis comprising a 1-DOF wrist and either a single- or a multi-DOF terminal device. For each test condition, we will train participants to use sequential PR control and perform initial functional testing using a comprehensive toolbox of outcome measures, compiled based on recommendations from the Academy of Prosthetics and Orthotics and our prior research experience. Participants will then take the prosthesis home and use it for everyday tasks for six weeks, allowing extensive practice to optimize their functional control of the device. At the end of the home trial, participants will perform the same outcome measures to assess function. We will repeat this sequence for Aim 2, where participants will evaluate the same two prostheses except with the 2-DOF wrist. Finally, for Aim 3, we will follow the same protocol to compare sequential and simultaneous PR control of a prosthesis with a 1-DOF hand and a 2-DOF wrist. We expect that both the 2-DOF wrist and the simultaneous PR control system will provide improved function over the 1-DOF wrist and sequential control, respectively. This study will provide a quantitative assessment of the benefits of a 2-DOF wrist and of simultaneous PR control, which is necessary for commercialization and further development of these technologies to improve prosthetic options, and functional ability, for individuals with transradial amputations.